Yang Mei, Li Jun, Wu Jun, Wang Hui, Guo Baoping, Wu Chuanchuan, Shou Xi, Yang Ning, Zhang Zhuangzhi, McManus Donald P, Zhang Fuchun, Zhang Wenbao
Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, 14 Shengli Road, Urumqi 830046, PR China - Basic Medical College of Xinjiang Medical University, Urumqi 830011, PR China.
State Key Laboratory of Pathogenesis, Prevention and Treatment of Central Asian High Incidence Diseases, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, PR China.
Parasite. 2017;24:36. doi: 10.1051/parasite/2017037. Epub 2017 Oct 3.
Cystic echinococcosis is an important parasitic zoonosis caused by the dog tapeworm Echinococcus granulosus. Little is known about adult worm development at the molecular level. Transcription analysis showed that the E. granulosus hormone receptor 3-like (EgHR3) gene was expressed in protoscoleces and adult worms, indicating its role in early adult development. In this study, we cloned and characterized EgHR3 showing that its cDNA contains an open reading frame (ORF) of 1890 bp encoding a 629 amino acid protein, which has a DNA-binding domain (DBD) and a ligand-binding domain (LBD). Immunolocalization revealed the protein was localized in the parenchyma of protoscoleces and adult worms. Real-time PCR analysis showed that EgHR3 was expressed significantly more in adults than in other stages of development (p<0.01) and that its expression was especially high in the early stage of adult worm development induced by bile acids. EgHR3 siRNA silenced 69-78% of the level of transcription in protoscoleces, which resulted in killing 43.6-60.9% of protoscoleces after 10 days of cultivation in vitro. EgHR3 may play an essential role in early adult worm development and in maintaining adult biological processes and may represent a novel drug or vaccine target against echinococcosis.
囊型棘球蚴病是由犬绦虫细粒棘球绦虫引起的一种重要的寄生性人畜共患病。在分子水平上,人们对成虫发育了解甚少。转录分析表明,细粒棘球绦虫激素受体3样(EgHR3)基因在原头节和成虫中表达,表明其在成虫早期发育中的作用。在本研究中,我们克隆并鉴定了EgHR3,结果显示其cDNA包含一个1890 bp的开放阅读框(ORF),编码一个629个氨基酸的蛋白质,该蛋白质具有一个DNA结合结构域(DBD)和一个配体结合结构域(LBD)。免疫定位显示该蛋白定位于原头节和成虫的实质组织中。实时PCR分析表明,EgHR3在成虫中的表达明显高于其他发育阶段(p<0.01),并且在胆汁酸诱导的成虫发育早期其表达尤其高。EgHR3 siRNA使原头节中的转录水平沉默了69 - 78%,在体外培养10天后导致43.6 - 60.9%的原头节死亡。EgHR3可能在成虫早期发育以及维持成虫生物学过程中发挥重要作用,并且可能代表一种针对棘球蚴病的新型药物或疫苗靶点。